4α-hydroxy-5α,6β,7α,11β-H-guaian-1(10)-en-6,12-olide | 35008-26-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酯类
• 英文名称: 4α-hydroxy-5α,6β,7α,11β-H-guaian-1(10)-en-6,12-olide
• 英文别名: (-)-4α-hydroxy-5,7αH,6,11βH-guai-1(10)-en-6,12-olide；(-)-11βH,13-dihydromicheliolide；11βH,13-dihydromicheliolide；(3S,3aS,9R,9aS,9bS)-9-hydroxy-3,6,9-trimethyl-3,3a,4,5,7,8,9a,9b-octahydroazuleno[4,5-b]furan-2-one
• CAS: 35008-26-5
• 化学式: C₁₅H₂₂O₃
• 分子量: 250.338
• InChiKey: HHXFJHUFULMWRU-HZQNPPOTSA-N

物化性质

• 熔点：
  124-127 °C
• 沸点：
  409.0±40.0 °C(Predicted)
• 密度：
  1.15±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  18
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4α-hydroxy-5α,6β,7α,11β-H-guaian-1(10)-en-6,12-olide 、 间氯过氧苯甲酸 生成 (1S,3R,6S,7S,10S,11S,12R)-12-hydroxy-3,7,12-trimethyl-2,9-dioxatetracyclo[9.3.0.01,3.06,10]tetradecan-8-one
  参考文献：
  名称：

  PARODI, FELIX J.;FRONCZEK, FRANK R.;FISCHER, NIKOLAUS H., J. NATUR. PROD., 52,(1989) N, C. 554-566

  摘要：

  DOI：
• 作为产物：
  描述：

  1β,4α-dihydroxy-3α,11β-H-eudesman-6α,12-olide 在 potassium acetate 作用下， 以 吡啶 、 溶剂黄146 为溶剂， 反应 98.0h， 生成 4α-hydroxy-5α,6β,7α,11β-H-guaian-1(10)-en-6,12-olide
  参考文献：
  名称：

  Biomimetic cyclization of gallicin to form guaianolides

  摘要：

  DOI：

  10.1016/0040-4020(80)80216-x

文献信息

• Sesquiterpene Lactones and Their Derivatives Inhibit High Glucose-Induced NF-κB Activation and MCP-1 and TGF-β1 Expression in Rat Mesangial Cells
  作者：Qian-Qian Jia、Jian-Cheng Wang、Jing Long、Yan Zhao、Si-Jia Chen、Jia-Dai Zhai、Lian-Bo Wei、Quan Zhang、Yue Chen、Hai-Bo Long

  DOI：10.3390/molecules181013061

  日期：——

  Diabetic nephropathy (DN) is one of the most common and serious chronic complications of diabetes mellitus, however, no efficient clinical drugs exist for the treatment of DN. We selected and synthesized several sesquiterpene lactones (SLs), and then used the MTT assay to detect rat mesangial cells (MCs) proliferation, ELISA to measure the expression level of monocyte chemoattractant protein-1 (MCP-1), transforming growth factor beta (TGF-β1) and fibronectin(FN), real-time fluorescent quantitative PCR analysis to measure the MCP-1 and TGF-β1 gene expression, western blot to detect the level of IκBα protein and EMSA to measure the activation of nuclear factor kappa B (NF-κB). We discovered that SLs, including parthenolide (PTL), micheliolide (MCL), arglabin, and isoalantolactone (IAL), as well as several synthetic analogs of these molecules, could effectively attenuate the high glucose-stimulated activation of NF-κB, the degradation of IκBα, and the expression of MCP-1, TGF-β1 and FN in rat mesangial cells (MCs). These findings suggest that SLs and their derivatives have potential as candidate drugs for the treatment of DN.

  糖尿病肾病（DN）是糖尿病最常见且严重的慢性并发症之一，但目前尚无有效的临床药物可用于DN的治疗。我们选择并合成了几种倍半萜内酯（SLs），然后使用MTT法检测大鼠系膜细胞（MCs）的增殖，采用ELISA法测量单核细胞趋化蛋白-1（MCP-1）、转化生长因子β（TGF-β1）和纤维连接蛋白（FN）的表达水平，利用实时荧光定量PCR分析测定MCP-1和TGF-β1基因表达，采用西方印迹法检测IκBα蛋白水平，电泳迁移率实验（EMSA）检测核因子κB（NF-κB）的活化。我们发现，倍半萜内酯（如巴特诺里德（PTL）、米克希而内酯（MCL）、阿尔格拉滨和异阿兰酯（IAL））及其几种合成类似物能够有效减弱高糖刺激下大鼠系膜细胞（MCs）中NF-κB的活化、IκBα的降解，以及MCP-1、TGF-β1和FN的表达。这些发现表明，倍半萜内酯及其衍生物具有作为DN治疗候选药物的潜力。
• Stereoselective Synthesis of (+)-11<b>β</b><i>H</i>,13-Dihydroestafiatin, (+)-11<b>β</b><i>H</i>,13-Dihydroludartin, (−)-Compressanolide, and (−)-11<b>β</b><i>H</i>,13-Dihydromicheliolide from Santonin
  作者：Victoria Bargues、Gonzalo Blay、Luz Cardona、Begoña García、José R. Pedro

  DOI：10.1021/np020109f

  日期：2002.11.1

  Starting from 2 and 3, obtained from santonin (1), we have synthesized natural guaianolides 4-7. Chemoselective epoxidation of 2 gave (+)-11betaH,13-dihydroestafiatin (4), and epoxidation of 3 followed by regioselective elimination of the hydroxyl group afforded (+)-11betaH,13-dihydroludartin (5). Sharpless' mild regioselective ring-opening of 4 and 5 followed by hydrogenolysis yielded (-)-compressanolide (6) and (-)-11betaH,13-dihydromicheliolide (7), respectively.
• Guaianolide Sesquiterpene Lactones, a Source To Discover Agents That Selectively Inhibit Acute Myelogenous Leukemia Stem and Progenitor Cells
  作者：Quan Zhang、Yaxin Lu、Yahui Ding、Jiadai Zhai、Qing Ji、Weiwei Ma、Ming Yang、Hongxia Fan、Jing Long、Zhongsheng Tong、Yehui Shi、Yongsheng Jia、Bin Han、Wenpeng Zhang、Chuanjiang Qiu、Xiaoyan Ma、Qiuying Li、Qianqian Shi、Haoliang Zhang、Dongmei Li、Jing Zhang、Jianping Lin、Lu-Yuan Li、Yingdai Gao、Yue Chen

  DOI：10.1021/jm301064b

  日期：2012.10.25

  Small molecules that can selectively target cancer stem cells (CSCs) remain rare currently and exhibit no common structural features. Here we report a series of guaianolide sesquiterpene lactones (GSLs) and their derivatives that can selectively eradicate acute myelogenous leukemia (AML) stem or progenitor cells. Natural GSL compounds arglabin, an anticancer clinical drug, and micheliolide (MCL), are able to reduce the proportion of AML stem cells (CD34(+)CD38(-)) in primary AML cells. Targeting of AML stem cells is further confirmed by a sharp reduction of colony-forming units of primary AML cells upon MCL treatment. Moreover, DMAMCL, the dimethylamino Michael adduct of MCL, slowly releases MCL in plasma and in vivo and demonstrates remarkable therapeutic efficacy in the nonobese diabetic/severe combined immunodeficiency AML models. These findings indicate that GSL is an ample source for chemical agents against AML stem or progenitor cells and that GSL is potentially highly useful to explore anti-CSC approaches.